JP2002504908A - 安定なインスリン製剤 - Google Patents
安定なインスリン製剤Info
- Publication number
- JP2002504908A JP2002504908A JP50323799A JP50323799A JP2002504908A JP 2002504908 A JP2002504908 A JP 2002504908A JP 50323799 A JP50323799 A JP 50323799A JP 50323799 A JP50323799 A JP 50323799A JP 2002504908 A JP2002504908 A JP 2002504908A
- Authority
- JP
- Japan
- Prior art keywords
- formulation
- buffer
- insulin
- tris
- monomeric insulin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 153
- 238000002360 preparation method Methods 0.000 title claims description 62
- 108090001061 Insulin Proteins 0.000 title claims description 39
- 102000004877 Insulin Human genes 0.000 title claims description 39
- 229940125396 insulin Drugs 0.000 title claims description 39
- 239000000203 mixture Substances 0.000 claims abstract description 127
- 238000009472 formulation Methods 0.000 claims abstract description 110
- 239000004026 insulin derivative Substances 0.000 claims abstract description 56
- 239000000872 buffer Substances 0.000 claims abstract description 36
- 239000007983 Tris buffer Substances 0.000 claims abstract description 33
- 239000004475 Arginine Substances 0.000 claims abstract description 19
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001802 infusion Methods 0.000 claims abstract description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 239000000243 solution Substances 0.000 claims description 37
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 35
- 229940048914 protamine Drugs 0.000 claims description 27
- 239000011701 zinc Substances 0.000 claims description 27
- 229910052725 zinc Inorganic materials 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 26
- 102000007327 Protamines Human genes 0.000 claims description 25
- 108010007568 Protamines Proteins 0.000 claims description 25
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 24
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 23
- 239000003755 preservative agent Substances 0.000 claims description 22
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 19
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 19
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- 235000011187 glycerol Nutrition 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
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- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 7
- 201000001421 hyperglycemia Diseases 0.000 claims description 7
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- 238000002156 mixing Methods 0.000 claims description 3
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 14
- 229930064664 L-arginine Natural products 0.000 description 13
- 235000014852 L-arginine Nutrition 0.000 description 13
- 235000009697 arginine Nutrition 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 230000003287 optical effect Effects 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 230000002776 aggregation Effects 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- 239000001488 sodium phosphate Substances 0.000 description 9
- 229910000162 sodium phosphate Inorganic materials 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 9
- 239000011787 zinc oxide Substances 0.000 description 9
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000013020 final formulation Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 230000000930 thermomechanical effect Effects 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
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- 238000004090 dissolution Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000012455 biphasic mixture Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
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- 238000007911 parenteral administration Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 3
- 229910001948 sodium oxide Inorganic materials 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 150000003751 zinc Chemical class 0.000 description 3
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 201000007131 Placental site trophoblastic tumor Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003017 phosphorus Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 229950008679 protamine sulfate Drugs 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 239000004246 zinc acetate Substances 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- BHHYHSUAOQUXJK-UHFFFAOYSA-L zinc fluoride Chemical compound F[Zn]F BHHYHSUAOQUXJK-UHFFFAOYSA-L 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010013457 Dissociation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- -1 Loin Chemical compound 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
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- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940127095 analogue insulin Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
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- 229960002242 chlorocresol Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5308997P | 1997-06-13 | 1997-06-13 | |
| US60/053,089 | 1997-06-13 | ||
| PCT/US1998/012218 WO1998056406A1 (fr) | 1997-06-13 | 1998-06-11 | Formulations d'insuline stables |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002504908A true JP2002504908A (ja) | 2002-02-12 |
| JP2002504908A5 JP2002504908A5 (fr) | 2005-12-22 |
Family
ID=21981869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50323799A Pending JP2002504908A (ja) | 1997-06-13 | 1998-06-11 | 安定なインスリン製剤 |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US6034054A (fr) |
| EP (1) | EP0884053B1 (fr) |
| JP (1) | JP2002504908A (fr) |
| KR (1) | KR100597500B1 (fr) |
| CN (1) | CN1293916C (fr) |
| AR (1) | AR012894A1 (fr) |
| AT (2) | ATE329612T1 (fr) |
| AU (1) | AU734781B2 (fr) |
| BR (1) | BR9810116B1 (fr) |
| CA (1) | CA2295140C (fr) |
| CO (1) | CO4750643A1 (fr) |
| CZ (1) | CZ299637B6 (fr) |
| DE (2) | DE69808695T2 (fr) |
| DK (1) | DK0884053T3 (fr) |
| EA (1) | EA002880B1 (fr) |
| ES (2) | ES2185113T3 (fr) |
| HK (1) | HK1030747A1 (fr) |
| HU (1) | HUP0002877A3 (fr) |
| ID (1) | ID24310A (fr) |
| IL (1) | IL133348A0 (fr) |
| NO (1) | NO996131L (fr) |
| NZ (1) | NZ501382A (fr) |
| PE (1) | PE79099A1 (fr) |
| PL (1) | PL194244B1 (fr) |
| PT (2) | PT884053E (fr) |
| SV (1) | SV1998000065A (fr) |
| TR (1) | TR199903036T2 (fr) |
| TW (1) | TW577753B (fr) |
| UA (1) | UA61109C2 (fr) |
| WO (1) | WO1998056406A1 (fr) |
| ZA (1) | ZA984697B (fr) |
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| JP4874989B2 (ja) * | 2004-11-22 | 2012-02-15 | ノヴォ ノルディスク アー／エス | 可溶性で安定なインスリン含有調合物 |
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| JP2012233003A (ja) * | 2002-05-07 | 2012-11-29 | Novo Nordisk As | 単量体インスリン及びアシル化インスリンを含む可溶性製剤 |
| JP2006511441A (ja) * | 2002-05-07 | 2006-04-06 | ノボ ノルディスク アクティーゼルスカブ | 単量体インスリン及びアシル化インスリンを含む可溶性製剤 |
| US8114959B2 (en) | 2003-06-03 | 2012-02-14 | Novo Nordisk A/S | Stabilized pharmaceutical peptide compositions |
| US8114833B2 (en) | 2003-11-20 | 2012-02-14 | Novo Nordisk A/S | Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices |
| US8748376B2 (en) | 2004-11-12 | 2014-06-10 | Novo Nordisk A/S | Stable formulations of peptides |
| JP4874989B2 (ja) * | 2004-11-22 | 2012-02-15 | ノヴォ ノルディスク アー／エス | 可溶性で安定なインスリン含有調合物 |
| US8263551B2 (en) | 2004-11-22 | 2012-09-11 | Novo Nordisk A/S | Soluble, stable insulin-containing formulations with a protamine salt |
| JP2012530768A (ja) * | 2009-06-26 | 2012-12-06 | ノボ・ノルデイスク・エー／エス | インスリン、ニコチンアミド及びアミノ酸を含む製剤 |
| JP2015071608A (ja) * | 2009-06-26 | 2015-04-16 | ノボ・ノルデイスク・エー／エス | インスリン、ニコチンアミド及びアミノ酸を含む製剤 |
| JP2016503784A (ja) * | 2012-12-19 | 2016-02-08 | ウォックハート リミテッド | ヒトインスリン又はその類似体もしくは誘導体を含む安定な水性組成物 |
| US11752198B2 (en) | 2017-08-24 | 2023-09-12 | Novo Nordisk A/S | GLP-1 compositions and uses thereof |
| US11318191B2 (en) | 2020-02-18 | 2022-05-03 | Novo Nordisk A/S | GLP-1 compositions and uses thereof |
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